Abstract
While host immune response is likely to be important for the prognosis of gastric cancer patients, detailed information on the T lymphocyte infiltration in different gastric cancer subtypes is lacking. Here, we studied the presence of CD3, CD8, and FOXP3 (Forkhead box p3) expressing T lymphocytes in a retrospective cohort of 190 intestinal gastric and gastroesophageal adenocarcinomas. The cancers represented four distinct molecular subtypes: Epstein-Barr virus–positive (EBV+), mismatch-repair-deficient (MMR-D), aberrant TP53, and the “other” subtype. The absolute numbers of CD3+, CD8+, and FOXP3+ T lymphocytes were analyzed in relation with these molecular subtypes and selected clinicopathological parameters. Overall, there was a large variation in the amount of infiltrating T lymphocyte in all molecular subtypes. Among the subtypes, EBV+ cancers differed from the other subtypes in increased lymphocyte infiltration and high CD8+/FOXP3+ ratio. While the TP53 aberrant subtype did not differ in the absolute amount of T lymphocyte, the ratio of CD8+/FOXP3+ and CD3+/FOXP3+ cells was highest in this subtype, possibly reflecting immunosuppression associated with genomic instability. Increased CD3+ and CD8+ T lymphocyte infiltrates were associated with better survival, and remained as independent prognostic factors in a multivariate analysis. This study is the first to investigate lymphocytic infiltration within four molecular subtypes of intestinal-type gastric cancer in a European cohort. The results provide an important addition to the current knowledge of T lymphocyte–dependent immune response in gastric cancer and its prognostic significance.
Highlights
Gastric cancer is the fifth most common cancer type globally, and the second most common cause of cancer death [1]
Distribution of the CD3, CD8, and FOXP3 T lymphocytes among intestinal-type adenocarcinomas and their association with the molecular subtypes (Ventana/Roche)
While recent studies have shown that intestinal-type gastric cancer consists of several molecular subtypes, the potential of the different subtypes to elicit host immune response is not well-known
Summary
Gastric cancer is the fifth most common cancer type globally, and the second most common cause of cancer death [1]. Virchows Arch (2021) 478:707–717 cancers can be further divided into different molecular subtypes. These subtypes include (1) Epstein-Barr virus (EBV)– associated cancers, (2) mismatch-repair-deficient (MMR-D) cancers, (3) cancers with TP53 aberration, and (4) cancers lacking any of the above features (“other”) [7]. While the original molecular classification is based on genomic analysis, it is possible to identify these subtypes by immunohistochemistry/in situ hybridization [8]. This method utilizes markers already used in clinical practice and is adaptable to diagnostic routine
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